A Demonstration of Rejuvenation in Old Human Cells

Today, we are going to have a look at a new study that shows that senescent, non-dividing aged cells can be somewhat restored to working order using a new technique.

Before we do that, let’s take a look at what senescent cells are and how cellular senescence protects us from cancer and other harmful diseases.

Cellular senescence protects us from damaged cells

Cellular senescence is a safety mechanism that removes aged and potentially damaged cells from circulation. Having mutated and otherwise damaged cells replicating indefinitely would be a recipe for disaster, so this safety system kicks in to shut down these cells and summon the immune system to dispose of them.

Senescent cells are cells that have ceased replicating in response to damage or environmental stimuli or cells that have reached their replicative limit and have critically shortened telomeres that signal the cells to shut down. Senescent cells do not replicate and generally destroy themselves by programmed cell death, which is known as apoptosis; in some cases, they evade this process and remain in situ, causing inflammation and secreting a range of toxic signals that poison the local tissue.

Over time, the number of senescent cells increases in tissue, leading to a rising background of chronic inflammation that causes the immune system to become increasingly dysfunctional, impairs tissue repair and drives the progression of multiple age-related diseases[1].

The most obvious solution to this problem is to remove these senescent cells periodically from the body, and the removal of senescent cells is exactly what Dr. Aubrey de Grey and the SENS Research Foundation have been proposing for over a decade. This has been the focus of much research in recent years, and a new class of therapies known as senolytics aims to do exactly this.

However, some researchers have been tinkering with ways to reverse senescence in cells instead of the more direct approach of removing the problem in the first place.

Reversing cellular senescence

This senescent state was once thought to be an irreversible process, and while this is certainly true during the normal processes of biology, it is not the case when science intervenes. Using cell reprogramming, cell fate can be changed and senescence can be reversed, as demonstrated once again in a new study that shows another technique to achieve this[2].

Senescence is not a one-way street, and a cell can be reprogrammed back to working order from senescence, provided the correct signals are given to it. In fact, a whole range of cell states can be programmed; it is just a case of working out the correct signals and manipulating the genetic machinery to get the result you want. This is no easy task despite the great progress that has been made in the understanding of cell fate in the last decade.

We now understand how to change some cell states quite well, and we have become adept at resetting some cells back to a pluripotent state. Similar to embryonic stem cells, these cells can then be guided down different paths to create new kinds of cells. More recently, we have discovered that cells do not even need to be reverted back to this pluripotent state; instead, they can be directly changed from one type to another without this additional step via the process of transdifferentiation.

Once cell fate is reprogrammed, senescent cells can be made to begin replicating again, and these cells can even operate at a functionally younger level, with a number of aging markers reversed. The researchers of this study have found another technique to restore senescent cells to work.

They exposed aged cells to analogs of the common supplement resveratrol, which caused splicing factors, which are progressively turned off as we age, to be turned back on. Within a few hours, the cells appeared younger and started to rejuvenate, behaving like younger cells and dividing again.

Conclusion

As interesting as this experiment is, is it really a good idea to bring back senescent cells from their arrested replicative state? Considering that senescent cells are generally senescent for a reason, it seems to be a less than wise approach.

Senescent cells may simply be senescent because they have reached their replicative limit, but they might also be damaged and could be harboring any number of mutations that caused them to shut down in the first place. These mutations could potentially cause them to become cancerous, and indeed, cellular senescence is designed to protect us from this.

So, this approach is a double-edged sword. On one hand, the potential for returning damaged cells to circulation will almost certainly increase the risk of cancer, but on the other hand, the harm that senescent cells cause via their inflammatory secretions is also significant.

It seems that there could be short-term benefits to restoring senescent cells to circulation due to removing their toxic secretions, but in the long term, the risks are not trivial. Senescent cells are generally likely to be damaged, and, really, instead of returning them to work, they should be destroyed as the body intended.

This is why the senolytic approach of destroying these cells offers the most robust and lower-risk option in dealing with senescent cells, and why, in our view, the approach here is inferior and a poor second-best choice in the long-term. If we can simply remove these aged, damaged cells, why would we bother to paper over the problem? The answer seems obvious.

As a scientific writer and a devoted advocate of healthy longevity technologies Steve has provided the community with multiple educational articles, interviews and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity reporter, Psychology Today and Singularity Weblog. He is a co-author of the book “Aging Prevention for All” – a guide for the general public exploring evidence-based means to extend healthy life (in press).